Spirogermanium was described by L. M. Rice et al.; see, e.g., U.S. Pat. No. 3,825,546 to Rice, which discloses the compound as a novel antihypertensive agent, and Rice et al., "Spirans XXII. Synthesis of 4,4-Dialkyl-4-germacyclo-hexanone and 8,8-Dialkyl-8-germaazaspiro-4.5!decanes," J. Heterocyclic Chem. 11:1041-1047 (1974), in which the biological properties of the compound are examined in further detail. Syntheses of spirogermanium and related compounds, including silicon-substituted azaspiranes, were also disclosed by Rice, and involve the use of what were apparently novel azaspirodione intermediates. ##STR1## Spirogermanium
The dimethyl, diethyl, dipropyl and dibutyl derivatives of spirogermanium were later shown to be useful in a variety of contexts, including treatment of hypercholesterolemia (U.S. Pat. No. 4,291,030 to Mulinos), arthritis (U.S. Pat. No. 4,468,393 to Geschickter; Badger et al., "Antiarthritic and Suppressor Cell Inducing Activity of Azaspiranes: Structure-Function Relationships of a Novel Class of Immunomodulatory Agents," J. Med. Chem. 33:2963-2970 (1990); DiMartino et al., "Antiarthritic and Immunoregulatory Activity of Spirogermanium," J. Pharmacol. and Exper. Theraipeutics 236(1):103-110)), and multiple sclerosis (U.S. Pat. No. 4,654,333 to Tenoso). Anticancer activity for spirogermanium itself has also been suggested; see, e.g., Mirabelli et al., "Pharmacological Activities of Spirogermanium and Other Structurally Related Azaspiranes: Effects on Tumor Cell and Macrophage Functions," Anti-Cancer Drug Design 3:231-242 (1989), Slavik et al., "Spirogermanium: A New Investigational Drug of Novel Structure and Lack of Bone Marrow Toxicity," Investigational New Drugs 1:225-234 (1983), and Badger et al., "Generation of Suppressor Cells in Normal Rats by Treatment with Spirogermanium, a Novel Heterocyclic Anticancer Drug," Immunopharmacology 10:201-207 (1985).
Spirogermanium is currently available from Unimed, Inc., as the hydrochloride salt, under the trademark SPIRO-32.RTM.. Spirogermanium HCl is a white powder which is freely soluble in water and in 95% ethanol, has a molecular weight of 414 and a melting point ranging from 284.degree. C. to 288.degree. C. Spirogermanium has been administered both by intravenous infusion and orally.
To date, topical administration of spirogermanium or related azaspirane compounds is unknown. The present invention is premised on the unexpected finding that topical administration of spirogermanium and related azaspiranes is extremely effective in addressing certain skin conditions associated with hyperproliferation of skin cells and/or an immunologically mediated disorder. specifically, it has now been discovered that spirogermanium and certain structurally related azaspiranes may be administered in topical formulations to prevent or treat a host of skin conditions, including psoriasis and various forms of dermatitis, including atopical dermatitis, contact dermatitis and seborrhoeic dermatitis.